55 The catalog of what is going on during depression is drawn from multiple sources too numerous to list, as well as from countless interviews with doctors, clinicians, and specialists. For superb and vivid descriptions of the basics of the majority of these processes see Peter Whybrow’s A Mood Apart, pages 150–67. The April 1999 edition of Psychology Today offers another summary of the biologies of depression. Charles Nemeroff’s summary of the neurobiology of depression, found in the June 1998 Scientific American, also provides a more detailed, nonacademic discussion of many of the complex issues brought up here.
56 The idea that raising levels of TRH can be a useful treatment in depression, at least temporarily, is spelled out in Fred Goodwin and Kay Jamison’s Manic-Depressive Illness, page 465.
56 There is now a large body of work to support the idea that depressions become more severe during a lifetime. I have discussed the matter in particular detail with Robert Post of the NIMH and John Greden of the University of Michigan.
56 The quotation from Kay Jamison is taken from Night Falls Fast, page 198.
56 The insight about seizures in the animal brain comes largely from the work of Suzanne Weiss and Robert Post. For information on the “kindling” phenomenon and its use as a model for affective disorders, see their coauthored article “Kindling: Separate vs. shared mechanisms in affective disorder and epilepsy,” Neuropsychology 38, no. 3 (1998).
57 The information on the lesioning of monoamine systems in animal brains comes from Juan López et al., “Regulation of 5-HT Receptors and the Hypothalamic-Pituitary-Adrenal Axis: Implications for the neurobiology of suicide,” Annals of the New York Academy of Sciences 836 (1997). On depression and the monoamine system and cortisol, see Juan López et al., “Neural circuits mediating stress,” Biological Psychiatry 46 (1999).
57 This explanation of stress responses in depression is based on the work of Juan López and Elizabeth Young at the University of Michigan, and Ken Kendler at the Medical College of Virginia in Richmond. There are as many explanations of depression as there are stars in the night sky, but I think the Michigan scientists’ stress-based model is particularly convincing.
58 For the study using ketoconazole on an experimental basis, see O. M. Wolkowitz et al., “Antiglucocorticoid treatment of depression: double-blind ketoconazole,” Biological Psychiatry 45, no. 8 (1999).
58 The studies on baboons were done by Robert Sapolsky and described to me in an oral interview with Elizabeth Young. The work on air traffic controllers may be found in R. M. Rose et al., “Endocrine Activity in Air Traffic Controllers at Work. II. Biological, Psychological and Work Correlates,” Psychoneuroendocrinology 7 (1982).
58 That the heart is weakened after a myocardial infarction is a well-established idea. However, the severity of damage done to the heart depends upon the size of the area of dead tissue within the heart. While the data indicate that isolation lesions don’t necessarily put one at a higher rate of relapse than controls, diffuse coronary disease almost certainly does. Nonetheless, close attention must be paid to the heart condition of anyone who has experienced a heart attack, and therapies to prevent relapse are in order for such a person. I thank Dr. Joseph Hayes of Cornell for his assistance with this matter.
59 Juan López’s work with the stress systems of rats may be found in Juan López et al., “Regulation of 5-HT1A Receptor, Glucocorticoid and Mineralocorticoid Receptor in Rat and Human Hippocampus: Implications for the Neurobiology of Depression,” Biological Psychiatry 43 (1998). The work on cortisol levels and adrenal enlargement postsuicide is found in Juan López et al., “Regulation of 5-HT Receptors and the Hypothalamic-Pituitary-Adrenal Axis: Implications for the Neurobiology of Suicide,” Annals of the New York Academy of Sciences 836 (1997).
60 Work on the effects of continued stress on the brain may be found in a number of articles, a large majority of them headed by Robert Sapolsky. For information on the brain’s response to stress, see Robert Sapolsky et al., “Hippocampal damage associated with prolonged glucocorticoid exposure in primates,” Journal of Neuroscience 10, no. 9 (1990). For studies concerning the interaction of biological stress and social status, see Robert Sapolsky, “Stress in the Wild,” Scientific American 262, no. 1 (1990), and his “Social subordinance as a marker of hypercortisolism: Some unexpected subtleties,” Annals of the New York Academy of Sciences 771 (1995). Greden’s discussion of the epidemiology of major depression is in Barbara Burns et al., “General Medical and Specialty Mental Health Service Use for Major Depression,” International Journal of Psychiatry in Medicine 30, no. 2 (2000).
60 The literature on antidepressants is based primarily on short-term studies and indicates that antidepressants take effect within two to four weeks and reach optimal function within six weeks. My own experience suggests strongly that it takes many months to get the full results of these medications.
60 That 80 percent of patients respond to medication but only 50 percent to any particular medication is spelled out in Mary Whooley and Gregory Simon’s “Managing Depression in Medical Outpatients,” New England Journal of Medicine 343, no. 26 (2000).
61 The friend to whom I allude here is Dièry Prudent, whose story is told in chapter 5.
62 That the first episode of depression is highly related to life events, with recurrent episodes being less dependent on such events is an idea first espoused by Emil Kraepelin in Manic-Depressive Insanity and Paranoia. This idea has been studied rather extensively with great consistency in the findings. One of the most recent studies—Ken Kendler et al., “Stressful life events and previous episodes in the etiology of major depression in women: An evaluation of the ‘kindling’ hypothesis,” American Journal of Psychiatry 157, no. 8 (2000)—reviews the literature on the subject, while finding in its own research “strong and consistent evidence for a negative interaction. That is, with each new previous depressive episode, the association between stressful life events and onsets of major depression became progressively weaker.”
62 George Brown’s work on the relationship between depression and loss is published in a variety of academic journals, a small selection of which are referenced in the bibliography. For a particularly good introduction to his work I would recommend his essay “Loss and Depressive Disorders,” published in Adversity, Stress and Psychopathology, edited by B. P. Dohrenwend.
63 This important idea from Kay Jamison is nicely summed up in a line from her book on suicide, Night Falls Fast: “The absolute hopelessness of suicidal depression is, by its nature, contagious, and it renders those who would help impotent to do so,” page 294.
65 Thomas Aquinas’s remarks on fear occur in his Summa theologiae I-II, q. 25, a. 4, vol. 6, page 187. For a reliable English translation, see his Summa Theologica: Complete English Edition in Five Volumes, q. 25, a. 4, vol. 2, pages 702 –3. I thank Dr. John F. Wippel and Dr. Kevin White from the Catholic University of America for help in locating, translating, and interpreting these passages.
65 The overlap among affective disorders, alcoholism, and genetics is extremely complicated. For an excellent summary of current positions, studies, and conclusions see Frederick Goodwin and Kay Jamison’s “Alcohol and Drug Abuse in Manic-Depressive Illness,” beginning on page 210 in their book Manic-Depressive Illness. I would also highly recommend David McDowell and Henry Spitz’s Substance Abuse and Marc Galanter and Herbert Kleber’s Textbook of Substance Abuse Treatment.
65 This statistic on anxiety disorder is taken from Stephen Hall, “Fear Itself,” New York Times Magazine, February 28, 1999, page 45.
65 For a more in-depth discussion of anxiety and sleep, see T. A. Mellman and T. W. Uhde, “Sleep and Panic and Generalized Anxiety Disorders,” in The Neurobiology of Panic Disorder, edited by James Ballenger.
66 The quote from Sylvia Plath is from The Bell Jar, page 3.
66 The Jane Kenyon quotation comes from “Having It Out with Melancholy” in the volume Constance, page 25.
77 The quotation from Daniil Kharms c
omes from Incidences, page 4.
78 The quotation from Artaud is taken from the title of one of his drawings. See the Artaud catalog from the Museum of Modern Art exhibition Antonin Artaud: Works on Paper, 1996.
78 The quotation from F. Scott Fitzgerald’s The Great Gatsby occurs on page 66.
79 The Jane Kenyon quotation comes from “Back” in the volume Constance, page 32.
85 The standard textbook on emergency medicine is titled Emergency Medicine: Concepts and Clinical Practice, 4th ed., 3 vols., edited by Peter Rosen et al.
CHAPTER III: TREATMENTS
101 The quotation from T. M. Luhrmann is in her remarkable book Of Two Minds, page 7.
102 For the Luhrmann quotation, see Ibid., 290.
103 The quotation from The Years may be found on page 378.
103 Russ Newman, the executive director for professional practice at the American Psychological Association, writes in a letter to the editor of U.S. News & World Report, April 26, 1999, “The research has been quite clear that in many cases of depression the treatment of choice is really ‘treatments of choice’: a combination of psychotherapy and medication,” page 8. A recent study has found similar results. See Martin Keller et al., “A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression,” New England Journal of Medicine 342, no. 20 (2000). For a summary of this study in the popular press, see Erica Goode, “Chronic-Depression Study Backs the Pairing of Therapy and Drugs,” New York Times, May 18, 2000. Ellen Frank has done a number of studies comparing talking and pharmaceutical therapies with different specific populations. Her geriatric study entitled “Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression,” Journal of the American Medical Association 281, no. 1 (1999), concludes, “Combined treatment using both [treatment strategies] appears to be the optimal clinical strategy in preserving recovery.” Initial studies in this area, such as Gerald Klerman et al., “Treatment of depression by drugs and psychotherapy,” American Journal of Psychiatry 131 (1974), and Myrna Weissman and Eugene Paykel, The Depressed Woman: A Study of Social Relationships, also point toward the improved efficacy of combination therapy.
107 The basic description of the methodology of CBT can be found in Beck’s seminal work, Depression. Among more contemporary publications, see especially Mark Williams’s The Psychological Treatment of Depression, 2nd edition.
107 The phrase “learned optimism” comes from Martin Seligman and is the title of his 1990 book.
109 The basic methodology of IPT is described thoroughly in Myrna Weissman, John Markowitz, and Gerald Klerman’s Comprehensive Guide to Interpersonal Psychotherapy.
111 The study concerning professors as therapists is Hans Strupp and Suzanne Hadley, “Specific vs. nonspecific factors in psychotherapy: A controlled study of outcome,” Archives of General Psychiatry 36, no. 10 (1979). They write, “The results of this investigation were consistent and straightforward. Patients undergoing psychotherapy with college professors showed, on average, quantitatively as much improvement as patients treated by experienced professional psychotherapists,” page 1134.
111 My discussion of the neurotransmitter levels of depressed people was garnered from books, articles, and interviews too numerous to mention. Many of these ideas, however, are elucidated clearly in Peter Whybrow’s A Mood Apart.
111 For a discussion of tryptophan and depression, see T. Delgado et al., “Serotonin function and the mechanism of antidepressant action: Reversal of antidepressant by rapid depletion of plasma tryptophan,” Archives of General Psychiatry 47 (1990), and K. Smith et al., “Relapse of Depression After Rapid Depletion of Tryptophan,” Lancet 349 (1997).
112 For an excellent and insightful examination of serotonin’s synthesis and function, see Peter Whybrow’s A Mood Apart, pages 224 –27.
112 Receptor theory is fully explicated in David Healy’s exceptional book The Antidepressant Era, pages 161 –63; 173–77.
112 The notion of indirect function for the drugs that effect neurotransmitters, and the problem of homeostasis, are discussed provocatively in Peter Whybrow’s A Mood Apart, pages 150 –67.
113 The effects of the SSRIs on REM sleep was described in Michael Thase’s presentation, “Sleep and Depression,” at APA 2000, the annual conference of the American Psychiatric Association, delivered on May 14, 2000, in Chicago. The effects of the SSRIs on brain temperature is part of the larger chemistry of depression. It has been noted that in depression the body’s temperature, especially at night, is often elevated. However, this elevation is only relative; the body’s temperature simply drops less at night in depression than it normally would. This higher nocturnal temperature in depression goes along with other measures of hyperarousal, such as insomnia. That antidepressants reduce this elevated temperature is probably good—a normalization, so to speak. Some of these points are discussed in a review chapter entitled “Biological Processes in Depression: An Updated Review and Integration,” by Michael Thase and Robert Howland in The Handbook of Depression, edited by E. Edward Beckham and William Leber, pages 213 –79.
113 Most of the information regarding animal studies, maternal separation, aggression, and altered neurobiology comes from the NIMH-sponsored “Suicide Research Workshop” held November 14–15, 1996. Much, however, has been published in this area in general. I would particularly recommend Gary Kraemer et al., “Rearing experience and biogenic amine activity in infant rhesus monkeys,” Biological Psychiatry 40, no. 5 (1996), as an introduction to the topic.
113 There has been much work on maternal separations and cortisol. See Gayle Byrne and Stephen Suomi, “Social Separation in Infant Cebus Apella: Patterns of Behavioral and Cortisol Response,” International Journal of Developmental Neuroscience 17, no. 3 (1999), and David Lyons et al., “Separation Induced Changes in Squirrel Monkey Hypothalamic-Pituitary-Adrenal Physiology Resemble Aspects of Hypercortisolism in Humans,” Psychoneuroendocrinology 24 (1999). That antidepressants can alleviate this condition is explicated in Pavel Hrdina et al., “Pharmacological Modification of Experimental Depression in Infant Macaques,” Psychopharmacology 64 (1979).
113 The work on dominant vervet monkeys is in Michael Raleigh et al., “Social and Environmental Influences on Blood Serotonin Concentrations in Monkeys,” Archives of General Psychiatry 41 (1984). That raising serotonin will alleviate these problems is discussed in Michael Raleigh and Michael McGuire, “Bidirectional Relationships between Tryptophan and Social Behavior in Vervet Monkeys,” Advances in Experimental Medicine and Biology 294 (1991), and Michael Raleigh et al., “Serotonergic Mechanisms Promote Dominance Acquisition in Adult Male Vervet Monkeys,” Brain Research 559 (1991).
114 The work on animal risk-taking, aggression, and serotonin can be found in P. T. Mehlman et al., “Low CSF 5-HIAA Concentrations and Severe Aggression and Impaired Impulse Control in Nonhuman Primates,” American Journal of Psychiatry 151 (1994).
114 The work on monkey rank and serotonin is reviewed in Michael McGuire and Alfonso Troisi’s Darwinian Psychiatry, pages 93 –94; 172–74.
114 The evidence that SSRIs can reverse patterns of aggression is in C. Sanchez et al., “The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice,” Psychopharmacology 110, no. 1–2 (1993).
115 There is some controversy regarding the frequency of side effects from many of the SSRIs, most notably Prozac. Most doctors and clinicians feel that the frequency of many of the side effects, especially reduced sexual drive and anorgasmia, was radically underestimated by the pharmaceutical companies in their initial testings.
115 The information from Anita Clayton is drawn from her presentation “Epidemiology, Classification, and Assessment of Sexual Dysfunction” delivered on May 13 at APA 2000 in Chicago.
116 The statistic on the discontinuation of antidepressants after six months comes from Dr. H. George Nurnberg’s presentation “M
anagement of Antidepressant-Associated Sexual Dysfunction” delivered on May 13 at APA 2000 in Chicago.
116 For this catalog of pro-sexual drugs, see Ibid.
117 For Viagra’s effect on nocturnal penile tumescence, see Ibid.
117 For the idea of taking Viagra daily, see Ibid.
117 Dr. Andrew Nierenberg presented his research in “Prevalence and Assessment of Antidepressant-Associated Dysfunction”; Dr. Julia Warnock presented her research in “Hormonal Aspects of Sexual Dysfunction in Women: Improvement with Hormone Replacement Therapy.” Both presentations were delivered on May 13 at APA 2000 in Chicago.
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